title: Microbial biofilms on the surface of intravaginal rings worn in non-human primates.
abstract: Millions of intravaginal rings (IVRs) are used by women worldwide for contraception and for the treatment of vaginal atrophy. These devices also are suitable for local and systemic sustained release drug delivery, notably for antiviral agents in human immunodeficiency virus pre-exposure prophylaxis. Despite the widespread use of IVRs, no studies have examined whether surface-attached bacterial biofilms develop in vivo, an important consideration when determining the safety of these devices. The present study used scanning electron microscopy, fluorescence in situ hybridization and confocal laser scanning microscopy to study biofilms that formed on the surface of IVRs worn for 28 days by six female pig-tailed macaques, an excellent model organism for the human vaginal microbiome. Four of the IVRs released the nucleotide analogue reverse transcriptase inhibitor tenofovir at a controlled rate and the remaining two were unmedicated. Large areas of the ring surfaces were covered with monolayers of epithelial cells. Two bacterial biofilm phenotypes were found to develop on these monolayers and both had a broad diversity of bacterial cells closely associated with the extracellular material. Phenotype I, the more common of the two, consisted of tightly packed bacterial mats approximately 5 µm in thickness. Phenotype II was much thicker, typically 40 µm, and had an open architecture containing interwoven networks of uniform fibres. There was no significant difference in biofilm thickness and appearance between medicated and unmedicated IVRs. These preliminary results suggest that bacterial biofilms could be common on intravaginal devices worn for extended periods of time.
authors.affiliation: Auritec Pharmaceuticals Inc., Suite 3, 1434 6th Street, Santa Monica, CA, USA.|Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: Manjula
authors.initials: M
authors.lastname: Gunawardana
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Moss
authors.affiliation: Department of Ophthalmology, University of Kentucky, Lexington, KY, USA.|Auritec Pharmaceuticals Inc., Suite 3, 1434 6th Street, Santa Monica, CA, USA.|Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Auritec Pharmaceuticals Inc., Suite 3, 1434 6th Street, Santa Monica, CA, USA.
authors.forename: Etana
authors.initials: E
authors.lastname: Kopin
authors.affiliation: Auritec Pharmaceuticals Inc., Suite 3, 1434 6th Street, Santa Monica, CA, USA.|Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: Cali
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Auritec Pharmaceuticals Inc., Suite 3, 1434 6th Street, Santa Monica, CA, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Malone
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rabe
authors.affiliation: Ahmanson Advanced EM & Imaging Center, House Ear Institute, 2100 W. 3rd Street, Los Angeles, CA, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaudinn
authors.affiliation: Ahmanson Advanced EM & Imaging Center, House Ear Institute, 2100 W. 3rd Street, Los Angeles, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Webster
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, TB Prevention, Coordinating Center for Infectious Diseases (CCID), Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, TB Prevention, Coordinating Center for Infectious Diseases (CCID), Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Sweeney
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, TB Prevention, Coordinating Center for Infectious Diseases (CCID), Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Oak Crest Institute of Science, 2275 E. Foothill Boulevard, Pasadena, CA, USA.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Baum
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification*; D044822:Biodiversity; D018441:Biofilms / Q000254:growth & development*; D003274:Contraceptive Devices, Female / Q000382:microbiology*; D003692:Delayed-Action Preparations; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D008254:Macaca nemestrina; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D063065:Organophosphonates / Q000493:pharmacokinetics; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine